Integrated Research Application System (IRAS) Question specific guidance Part B Section 3 Exposure to ionising radiation The following document collates all guidance for the questions in Part B: Section 3 Exposure to ionising radiation. Content 1. Introduction 2. Question A1 Details of radioactive materials 3. Question B1 Details of other ionising radiation 4. Questions C1 C3 Dose and risk assessment 5. Questions D1 D3 Clinical assessment Introduction The design of this section of IRAS and the accompanying guidance have been drawn up in consultation between the following bodies: Health Protection Agency, Medical Exposure Department (HPA RPD MED) on behalf of DH British Institute of Radiology (BIR) Radiation Protection Committee Institute of Physics and Engineering in Medicine (IPEM) Special Interest Groups for diagnostic radiology, radiation protection and nuclear medicine Royal College of Radiologists British Nuclear Medicine Society Society of Radiographers Administration of Radioactive Substances Advisory Committee (ARSAC) NHS R&D Forum National Research Ethics Service (NRES). Part B Section 3 of IRAS is divided into two parts, relating to radioactive materials and other ionising radiation respectively. Where the research involves administration of radioactive materials which are additional to normal care, nuclear medicine professionals at each site will require a research ARSAC certificate. The ARSAC application form can be launched from the Site Specific Information Form for the site. Most of the information required is populated automatically from Part A and Part B Section 3 of IRAS when completed. The risk assessment should be completed with input from health professionals with the appropriate expertise to act as the lead Medical Physics Expert (MPE) and lead Clinical Radiation Expert (CRE) for the purposes of the application. Where the research involves different modalities and requires input from other experts, the lead experts should incorporate their advice into a single combined assessment. Integrated Research Application System (IRAS) 1
The information provided in this section should cover the potential range of exposure at all study sites participating in the research. A detailed guidance document on approval of research involving ionising radiation has been developed in consultation with the organisations listed above. It is available on the NRES website at: http://www.nres.npsa.nhs.uk/rec community/guidance/#ionisingrad. Question A1 Details of radioactive materials Please provide full information about each radioactive material being used. Where there is more than one radionuclide, generate a separate table. Notes on the table: Investigation: the investigation employing radioactive materials which is included in the study protocol. Radionuclide: the material which will be used. Proposed activity: the quantity which will be used in an individual investigation expressed in Microbecquerels (MBq). Route: the route by which the material will be given, e.g. intravenous, oral. Number of administrations: the number of individual investigations specified by the protocol for each study participant. Effective dose or target tissue dose: refer to Annex II of the ARSAC Notes for Guidance, available at http://www.arsac.org.uk/ The information should match the information about these investigations included in Question 19 of Part A of IRAS ("Details of clinical interventions and procedures"). Question B1 Details of other ionising radiation Provide full information about any other ionising radiation not listed in A1, i.e. other than radioactive materials. List each procedure required in the study protocol and, against each, specify: Number of procedures: the number of individual examinations specified by the protocol for each study participant Estimated procedure dose: the estimated dose per examination calculated by the lead MPE. The information should match the information about these investigations included in Question 19 of Part A of IRAS ("Details of clinical interventions and procedures"). Questions C1 C3 Dose and risk assessment Integrated Research Application System (IRAS) 2
Identifying a lead Medical Physics Expert (MPE) The role of lead Medical Physics Expert should be undertaken by a MPE who is a registered health professional and has expertise relevant to the proposed procedures. MPEs are usually registered as clinical scientists by the Health Professions Council under the Health Professions Order 2001. The Chief Investigator may wish to approach a colleague at the lead site to undertake the role of lead MPE. If a suitable individual is not available, it is acceptable for the role to be undertaken by a registered health professional at another research site or who is not involved at any site, provided they are suitably qualified. It is the responsibility of the Chief Investigator to ensure that the person appointed has appropriate expertise. Where more than one modality (imaging method) is involved, advice from more than one MPE may be required. The lead MPE should produce a combined assessment, giving the names of any other MPEs who have contributed to the assessment in Question C1. It is not essential for the lead MPE to be independent of the research team. It is not essential for the lead MPE to be employed by the NHS. The role may be undertaken by a suitably qualified registered health professional working in the private sector. However, the lead MPE should always be professionally based in the United Kingdom, as the role requires expertise in the UK regulatory and clinical environment. Assessment by the lead MPE The lead MPE should perform a dose/risk assessment of the proposed investigations for inclusion in sub section C1. It is helpful if the MPE has seen a copy of the lead CRE's clinical assessment beforehand. It is important that the assessment is included in the on line form rather than submitted in enclosures. This will facilitate access to the information by NHS R&D offices and radiation professionals at each research site. In the case of radioactive materials, the assessment will also be populated to the ARSAC research application form. The lead MPE should calculate appropriate doses for the proposed examinations, estimating the Total Research Protocol Dose and the element that is potentially additional to normal clinical exposure. The assessment should also include information about risks to facilitate the REC's deliberations as follows: Risks should be quantified where possible, referencing risk co efficients used (e.g. HPA, ICRP). The risk assessment should take into account the population being irradiated. Any adjustments made to these co efficients (e.g. to take account of a paediatric cohort) must be clearly stated. Any risk model used should be referenced (e.g. BEIR VII). The clinical prognosis of the study cohort should be taken into account when assessing risk, either following a risk calculation that excluded prognosis to place the risk in context, or as part of the risk assessment model. Integrated Research Application System (IRAS) 3
A risk statement should be included that gives an appropriate risk comparator, i.e. compares a radiation risk with an activity that has an appropriately similar level of risk. The lead MPE may also advise the Chief Investigator on the explanation of risks in the participant information sheet, practical aspects of the examinations, additional statutory requirements and any resource/organisational issues at research sites. The dose assessment should facilitate local IRMER compliance at participating sites by: Setting a Total Research Protocol Dose (TRPD) for the whole study. Assessing additional radiation dose based upon the lead CRE's statement on normal/additional exposures. Using national Diagnostic Reference Levels (DRLs) for examination dose where available, or an estimated dose to a standard patient. Where estimated, the methodology must be stated. Under IRMER, it is the role of the local MPE at each site to help establish the dose constraint or target dose level. However, the assessment by the lead MPE will facilitate this process by proposing for ethical approval an approximate total dose for an average patient for the whole study (TRPD), along with an order of magnitude risk from this dose. This will establish a level of exposure that is ethically acceptable while allowing for reasonable variation around this level. It is therefore important for the lead MPE to take account of potential variations in dose arising from differences both in examination protocols and in what constitutes normal practice among participating UK sites, using DRLs where appropriate. This will ensure that the main REC is fully appraised of the potential additional radiation burden to participants and how it may vary from centre to centre. The lead MPE may wish to consult colleagues at other sites that will be taking part in the study. Where the study involves changes in therapeutic dose or volume delivered, the lead Clinical Radiation Expert (CRE) will advise on the expected therapeutic outcome compared to standard protocols. The lead MPE can also provide relevant patient dosimetry advice and predictions of radiobiological effectiveness of all additional exposures associated with a patient treatment which does not follow standard protocols, even if the therapy dose itself does not change. The assessment should include consideration of doses as part of the treatment planning process (for instance an imaging modality such as PET CT for tumour delineation) or the verification process (such as Image Guided Radiotherapy). The lead MPE's assessment should be copied to the lead CRE, who should check that his/her advice remains valid in the light of the detailed dose and risk assessment. Radioactive materials rare or unusual substances If it is proposed to administer rare or unusual radioactive substances the following information is required by ARSAC and should be included in the dose/risk assessment: The formula of the substance and the site of its label. A summary of the animal (and any human) experiments and the bio distribution data obtained. A description of the method use in estimating the effective dose. Integrated Research Application System (IRAS) 4
Questions D1 D3 Clinical assessment Identifying a lead Clinical Radiation Expert The lead CRE should be a registered health professional with clinical expertise in the modality (imaging method) involved in the study. For radioactive materials exposure this will typically be a Nuclear Medicine Specialist. For other ionising radiation the CRE could be a radiologist or a clinical oncologist (for radiotherapy). The CI will often wish to approach a colleague at the lead site to undertake the role of lead CRE. If a suitable individual is not available, it is acceptable for the role to be undertaken by a registered health professional at another research site or who is not involved at any site, provided they are suitably qualified to give expert advice. It is the responsibility of the CI to ensure that the person appointed has appropriate expertise. Where the study involves different types of exposure (for example, both radiotherapy and other ionising radiation), advice may need to be sought from other CREs with relevant expertise. The lead MPE should produce a combined assessment, giving the names of any other CREs who have contributed to the assessment. It is not essential for the lead CRE to be independent of the research team. It is not essential for the lead CRE to be employed by the NHS. The role may be undertaken by a suitably qualified registered health professional at a private hospital or independent sector treatment centre. However, the lead CRE should always be professionally based in the United Kingdom, as the role requires expertise in the UK regulatory and clinical environment. Assessment by lead CRE The Chief Investigator should submit a draft of the application form, study protocol and participant information sheet to the lead CRE(s) who should: Review the proposed investigations/procedures (as summarised in question A19 in IRAS and in Questions A1 and B1 in this section) Assess whether the exposures in the protocol would exceed the exposures performed under existing clinical protocols as part of normal clinical management at any site in the study Where additional exposures could be involved, give advice in sub section D2 on their suitability to the objectives of the study and ethical acceptability. It is important that the assessment is included in the on line form rather than submitted in enclosures. This will facilitate access to the information by NHS RDoffices and radiation professionals at each research site. In the case of radioactive materials, the assessment will also be populated to the ARSAC research application form. In undertaking the assessment, the lead CRE should consider: The specific objectives of the exposure and the characteristics of the research population Integrated Research Application System (IRAS) 5
The potential diagnostic or therapeutic benefits, including direct benefits to the participant and the benefits to society The detriment to participants that the exposure may cause The availability of alternative techniques involving less, or no, exposure to ionising radiation The possibility that participants will be participating in other trials involving additional radiation. (Refer to questions 17 and 32 in Part A of IRAS for the selection criteria and details of possible involvement in other research.) The characteristics of the research population will include such factors as the age of the participants and their likely life expectancy. For multi site trials, variations in normal practice around the UK will have a bearing on whether or not the planned exposures represent an additional radiation burden for participants. The lead CRE should take such variations into account in making his/her assessment. Where any additional exposure is involved in the study, the assessment should provide a quantitative estimate of the range of normal/additional exposures across the study sites. To achieve this, it may be helpful to consult Practitioners and Medical Physics Experts at other research sites. Where existing clinical guidelines have been used in reaching a judgement about normal/additional exposures, these should be referenced. Participant information sheet The lead CRE should review the information sheet for participants and ensure that it contains accurate and appropriate advice on radiation exposure. In particular: Where there is no direct benefit to the participant, this should be made clear. The risks are realistic and not over or under stated. The information is comprehensible to participants It is sensitive to cohort prognosis by taking into account the population and illness under study 'Raw' numerical risks are not quoted without reference to reasonable comparators, and terminology is harmonised by reference to tables such as the HPA table in their patient information leaflet concerning x rays: http://www.hpa.org.uk/webc/hpawebfile/hpaweb_c/1194947388410 Liaison with lead MPE The lead CRE should copy the assessment to the lead MPE for the research. Co operation with the lead MPE during protocol development will ensure that any variations in clinical practice are taken into account by the lead MPE when preparing the dose and risk assessment for ethical review. IRAS QSG Part B Section 3 Version 2.0 Updated December 2008 Integrated Research Application System (IRAS) 6